Chloroquine for treatment of COVID-19 - a pig in a poke?

  1. R.J. Brüggemann
  2. D.J.A.R. Moes
  3. K.P. van Rhee
  4. N.E. van ’t Veer
  5. B.C.P. Koch
  6. M. van Rossum
  7. A. Vermeulen Windsant - van den Tweel
  8. M.H.E. Reijers
  9. R.R.J. van Kimmenade
  10. J.C. Rahamat- Langedoen
  11. T.C.D. Rettig
  12. R. van Raalte
  13. J. van Paassen
  14. F.N. Polderman
  15. P.D. van der Linden
  16. T. Frenzel
  17. Q. de Mast
  18. D.M. Burger
  19. J. Schouten
  20. F.L. van de Veerdonk
  21. P. Pickkers
  22. R. ter Heine
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Abstract

Objective

Chloroquine has been frequently administered for treatment of coronavirus disease 2019 but there are serious concerns about its efficacy and cardiac safety. Our objective was to investigate the pharmacokinetics and safety of chloroquine in hospitalized COVID-19 patients.

Design

A prospective observational study.

Setting

Dutch hospitals

Patients

Patients admitted to the hospital for treatment of COVID-19.

Interventions

Pharmacokinetic sampling

Measurements

The plasma concentrations of chloroquine and desethylchloroquine and QTc time.

Main Results

A total of 83 patients were included. The median (IQR) plasma concentration chloroquine during treatment was 1.05 μmol/L (0.63 - 1.55 μmol/L). None of the patients reached exposure exceeding the concentration to inhibit SARS-CoV-2 replication by 90% (IC90) of 6.9 μM. Furthermore, ΔQTc >60 milliseconds occurred after initiation of chloroquine treatment in 34% patients and during treatment QTc ≥500 milliseconds was observed in 46% of patients.

Conclusions

Recommended dose chloroquine treatment results in plasma concentrations that are unlikely to inhibit viral replication. Furthermore, the incidence of QTc prolongation was high. The preclinical promise of chloroquine as antiviral treatment in patients with COVID-19 is overshadowed by its cardiac toxicity and lack of effective exposure. It is unlikely that a positive clinical effect will be found with chloroquine for treatment of COVID-19.

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